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We sought to determine if altered electroencephalography (EEG) activities, such as delta band activity, in specific brain regions are associated with psychotic symptoms. Data were obtained from 17 neuroleptic-naive patients with schizophrenia and age- and sex-matched 17 healthy control subjects. Low Resolution Brain Electromagnetic Tomography (LORETA) was used to generate current source density images of delta, theta, alpha, and beta activities. Localization of the difference in EEG activity between the two groups was assessed by voxel-by-voxel non-paired t-test of the LORETA images. Spearman's correlation coefficient was obtained to relate LORETA values of EEG current density in brain regions showing a significant between-group difference and psychopathology scores. Delta band activity, represented by LORETA current density, was greater for patients in the following areas; the left inferior temporal gyrus, right middle frontal gyrus, right superior frontal gyrus, right inferior frontal gyrus, and right parahippocampal gyrus. LORETA values for delta band activity in the above five brain regions were negatively correlated with negative, but not positive symptoms. The results of this study suggest the role for electrophysiological changes in some of the brain regions, e.g. prefrontal cortex, in the manifestation of negative symptoms.

The purpose of this study was to determine if the functional single nucleotide polymorphisms of rs6259 C(-1019)G in the promoter region, which regulates serotonin 5-HT1A receptor transcription, affects the ability of antipsychotic drugs to improve attention in patients with schizophrenia. Subjects were neuroleptic-free and meeting DSM-IV-TR criteria for schizophrenia. Psychopathology and attention were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline and 3 months after treatment with atypical antipsychotic drugs (AAPDs). DNA was extracted from peripheral blood following standard procedures. Genotyping was performed with HS-Taq assay (LaboPass™). Data were available from 30 subjects (male/female=19/11), in which 17 had the CC genotype, three had the GG genotype, and 10 were heterozygous. The 3-month treatment with AAPDs was associated with significant improvements in positive and negative symptoms, but not attention as measured by SANS-Attention subscale in the entire subject group. There were no significant differences in the degree of improvements of SAPS and SANS scores between the CC genotype group and the (C/G plus G/G) combined group. On the other hand, improvement of attention was significantly greater for the former group compared to the latter group (P

Two third-generation aromatase inhibitors, letrozole and anastrozole, and the antiestrogen tamoxifen, were compared for growth-inhibiting activity in two estrogen receptor (ER)-positive aromatase-overexpressing human breast cancer cell lines, MCF-7aro and T-47Daro. Inhibition of hormone (1 nM testosterone)-stimulated proliferation was evaluated in both monolayer cultures and in three-dimensional spheroid cultures. Letrozole and anastrozole were also compared for effectiveness of aromatase inhibition, and relative affinity for aromatase, under both monolayer and spheroid growth conditions. Letrozole was an effective inhibitor of MCF-7aro monolayer cell proliferation, with an estimated 50% inhibitory concentration (IC50) of 50-100 nM, whereas an IC50 was not reached with anastrozole at any concentration tested (100-500 nM). An IC50 of tamoxifen was 1000 nM. Proliferation of T-47Daro monolayer cells was more sensitive to inhibition by all three agents; as with MCF-7aro cells, letrozole was the most effective inhibitor. MCF-7aro spheroids were slightly less sensitive than monolayer cells proliferation-inhibiting effects of letrozole (IC50 about 200 nM), and there was no significant inhibition with 100-200 nM anastrozole or 200-1000 nM tamoxifen. Letrozole and anastrozole significantly inhibited T-47Daro spheroid cell proliferation, at 15-25 and 50 nM, respectively, consistent with the greater sensitivity of T-47Daro monolayer cells to inhibition of proliferation by these agents. Tamoxifen failed to significantly inhibit T-47Daro spheroid cell proliferation over a 100-500 nM concentration range. Determination of aromatase inhibition in monolayers of both cell lines by a direct-access microsomal assay and an intact-cell assay revealed that letrozole was more active than anastrozole in monolayers of both cell lines and in both assays. In MCF-7aro spheroids following cell lysis, only letrozole significantly inhibited aromatase activity, supporting the conclusion that letrozole binds stronger to aromatase than anastrozole does. Our results demonstrate that MCF-7aro and T-47Daro spheroids could be a suitable model for evaluation of growth-inhibitory effects of agents used in hormonal therapy of breast cancer.

Aromatase (CYP19) is the estrogen synthetase that converts androgen to estrogen. The expression of aromatase in breast cancer cells and surrounding stromal cells is up regulated compared to non-cancerous cells. In situ estrogen synthesis is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner. A complex mechanism is involved in the control of human aromatase expression, in that seven promoters have been identified and found to be utilized in a tissue-selective manner. Increased aromatase expression in breast tumors is, in part, attributed to changes in the transcriptional control of aromatase expression. While promoter I.4 is the main promoter that controls aromatase expression in non-cancer breast tissue, promoters II and I.3 are the dominant promoters that drive aromatase expression in breast cancer tissue. During the last several years, our laboratory performed a series of studies to examine the transcription regulatory mechanism of aromatase expression in breast cancer cells. We functionally characterized promoters II and I.3, and carried out DNase 1 footprinting analysis that identified two regulatory elements, S1 and CREaro. Using the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA expression library, we found that four orphan/nuclear receptors, ERR alpha-1, EAR-2, COUP-TFI and RAR gamma, bind to the S1 element, and that CREB1, Snail (SnaH) and Slug proteins bind to the CREaro element. Studies from this and other laboratories have revealed that in cancer tissue versus normal tissue, several positive regulatory proteins (e.g. ERR alpha-1 and CREB1) are present at higher levels and several negative regulatory proteins (e.g. EAR-2, COUP-TFI, RAR gamma, Snail and Slug proteins) are present at lower levels. This may explain why the activity of promoters II and I.3 is up regulated in cancer tissue. An understanding of the molecular mechanisms of aromatase expression between non-cancerous and cancerous breast tissue, at the transcriptional level, may help in the design of a therapy based on the suppression of aromatase expression in breast cancer tissue.

Hafnium hydride was generated by the transmetalation between Bu 3 SnH and HfCl 4 using either THF or EtCN as the sol- vent. This process effectively reduced aldehydes, aldimines, ketones, and esters. In the hafnium hydride reduction of α-alkoxyketones, the diastereoselectivity was dependent on whether THF or EtCN was used as the solvent.

Fractionation with reverse-phase HPLC and electrophoretic analyses revealed that the nuclear basic proteins in sperm of an anuran amphibian, Discoglossus pictus, consisted of weakly basic proteins without histones. Amino acid analyses indicated that none of these proteins were histones or protamines because of the low amounts of Lys and Arg. The predominant protein among those fractionated possessed an unusually high content of His and extremely low amounts of Arg and Lys, indicating that this is a unique nuclear basic protein not reported previously. The induction of a highly decondensed state of sperm nuclei upon their incubation in egg extract was accompanied by the removal of most, if not all, of this His-rich protein from the nuclei.

We compare the physicochemical and functional characteristics of nucleoplasmin obtained from Xenopus laevis oocytes and by bacterial overexpression of a plasmid containing the nucleoplasmin gene. The comparison shows that, while the secondary structure of the protein is not affected by the method used to obtain this protein, the bacterial expressed form exhibits a marked tendency to form large aggregates and an impaired ability to displace protamines from sperm nuclei. These results add a word of caution to the indiscriminate use, in functional or structural (crystallographic) studies, of bacterially overproduced proteins that have been end-terminally tagged with polyhistidine.

A model is developed for determining the farfield strains in laminated composites from the strain values indicated by a microsensing device embedded inside the material. The microsensing device considered here consists of three elements: a sensor, a circuit chip, and an antenna. The sensor detects changes in the strains in the material surrounding the sensor. The circuit chip processes the sensor signals which are then transmitted, via the antenna, to a receiver located outside of the composite. The sensor and the circuit are powered by electromagnetic waves generated outside the material and transmitted to the antenna. The model proposed provides a means by which the signal emitted by the microsensing device, and picked up by a receiver, is converted to the engineering value of the farfield strain, i.e., to the strain which would exist in the material at the location of the sensor if the sensor were not present. On the basis of the model, two computer codes were written. The first code calculates the influence coefficient matrix, which is the parameter required to convert the sensor strain to the farfield strain; the second gives the farfield strain directly from the measured sensor strain. Tests were performed to verify the model and the computer codes. In these tests, a strain gauge, a rectangular steel plate, and a circular steel disk (simulating the components of a microsensing device) were embedded in a glass/epoxy beam. The sensor strains were measured by the embedded sensor; the farfield strains were measured by two surface mounted sensors. The measured farfield strains were compared to the farfield strains calculated by the present model, and good agreements were found between the measured and calculated farfield strains.

Nucleoplasmin was isolated from Xenopus laevis eggs and purified by an improved method using an open column. Its conformation was investigated spectrophotometrically by UV, CD and fluorescence. It was shown that alpha-helix content of nucleoplasmin was 30-40%, and one of the two tryptophan residues in nucleoplasmin located in the hydrophobic surroundings and the other in the relatively hydrophilic surroundings. The isolated nucleoplasmin was found to decondense sperm nuclei of salmon also, suggesting a possibility of the existence of nucleoplasmin-like protein in fish as well. Collapse of the protamine (salmine)-DNA complex as a simple model for fish sperm nuclei by nucleoplasmin was directly observed by measuring OD320 of aqueous protamine-DNA mixtures. This is a molecular level observation for the removal of protamine from DNA-protamine complex.

An operator cognitive model has been constructed referring to Rasmussen's ladder model, and a simulation system of operator performance has been developed. Computer simulation was then performed to investigate subjects' behavior in a cognitive experiment concerning PWR nuclear power plant diagnosis. The knowledge bases used in the simulation were constructed from the interview to the subjects. Confidence on each hypothesis and performance history of operators were compared between the experiment and the simulation, and the simulation could well explain the behavior of the subjects in the results of event identification, confidence on the results, hypotheses conceived during diagnosis, and plant parameters observed, which indicates the validity of the operator model. The order of parameter observation, however, disagreed, and it has been clearly shown that knowledge on system configuration of the plant as well as the physical layout of interface should be considered.

In this paper, a method of human cognitive state estimation based on physiological measures has been applied to the analysis of cognitive behavior during anomaly diagnosis observed with nuclear power plant simulator. This method has also been combined with the conventional experimental protocol such as operational sequence and questionnaire results. The simulator experiments have been performed using plant experts and the results demonstrate that the cognitive state estimation method can be an effective way for understanding cognitive behavior during the anomaly diagnosis of the nuclear power plant. It has also been shown from the results that the combined use of the human cognitive state estimation and the conventional experimental protocol can provide effective information in decreasing the ambiguity of the analysis results.

The molecular events associated with decondensation of human sperm nuclei were analyzed by incubating sperm with egg extracts from an amphibian, Bufo japonicus. Acid-urea-Triton polyacrylamide gel electrophoresis (AUT-PAGE) showed that the nuclear basic proteins of human sperm consist mainly of protamines (HPI, HPII) with minor amounts of nucleosomal histones. On incubation of lysolecithin (LC)- and dithiothreitol (DTT)-treated human sperm with the egg extract, the nuclei lost HPI and HPII within 15 min in association with extensive nuclear decondensation, and the acquirement of a whole set of nucleosomal histones. Incubation of LC-DTT-sperm with nucleoplasmin purified from Bufo eggs also induced nuclear decondensation and loss of protamines within 30 min. Native-PAGE and Western blot analyses of incubation medium indicated tight association of the released protamines to nucleoplasmin, strongly suggesting that protamines are removed from sperm nuclei not enzymatically but by their specific binding to nucleoplasmin. On incubation of LC-DTT-sperm with nucleoplasmin and exogenous nucleosomal core histones, micrococcal nuclease-protected DNA fragments were released, although their unit repeat length was slightly less than that of somatic nucleosomes. Thus remodeling of human sperm during fertilization can be mimicked under defined conditions with nucleoplasmin and exogenous histones.

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3 months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

The purpose of this study was to determine if perospirone, a second generation antipsychotic drug and partial agonist at serotonin-5-HT(1A) receptors, enhances electrophysiological activity, such as event-related potentials (ERPs), in frontal brain regions, as well as cognitive function in subjects with schizophrenia. P300 current source images were obtained by means of standardized low resolution brain electromagnetic tomography (sLORETA) before and after treatment with perospirone for 6 months. Perospirone significantly increased P300 current source density in the left superior frontal gyrus, and improved positive symptoms and performance on the script tasks, a measure of verbal social cognition, while verbal learning memory tended to be improved. There was a significant correlation between the changes in P300 amplitude on the left frontal lead and those in social cognition. These results suggest the changes in three-dimensional distribution of cortical activity, as demonstrated by sLORETA, may mediate some of the actions of antipsychotic drugs. The distinct cognition-enhancing profile of perospirone in patients with schizophrenia may be related to its actions on 5-HT(1A) receptors.

We have investigated the activity and expression of aromatase enzyme in nontumoral, cirrhotic, and malignant human liver tissues and cells using both chromatographic and reverse transcription (RT)-PCR analyses. After 24- and 72-h incubation of tissue minces or hepatic cell lines with either testosterone or androstenedione as androgen precursor, human hepatocellular carcinoma (HCC) tissues and HepG2 hepatoma cells showed elevated aromatase activity, with estrogen formation rates being 20 and95%, respectively, as opposed to nontumoral hepatic tissues and nonmalignant Chang liver (CL) cells, where no aromatase activity could be detected. Cirrhotic samples exhibited intermediate enzyme activity. Notably, exposure of HepG2 cells to the aromatase inhibitor Letrozole resulted in a striking decrease of estrogen formation, which became virtually absent at a Letrozole dose of 0.4 nM. RT-PCR analysis revealed markedly lower aromatase mRNA in both CL cells and nontumoral liver tissues, as compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels, in turn comparable with those observed in nontumoral or HCC tissues. Exon-specific RT-PCR showed prominent expression of exon I.3A-containing message and exon I.4-containing message in CL and HepG2 cells, as in nontumoral and HCC tissues, respectively. The present evidence implies that locally elevated estrogen formation in malignant human liver tissues and cells may have a role in the development and/or maintenance of human HCC, eventually leading to develop alternative strategies for treatment of HCC patients using antiaromatase agents.

Aromatase plays an important role in breast cancer development through its role in the synthesis of estrogen. Aromatase expression in breast tissue can be regulated by several mechanisms. The major promoter usage for aromatase expression in breast tumors (i.e. cAMP-stimulated promoters I.3 and II) is different from that in normal breast tissue (i.e. glucocorticoid-stimulated promoter I.4). Recent characterization of transcription factors that interact with the two important regulatory elements near promoters I.3 and II, i.e. S1 and CREaro, helps us better understand the mechanism of the switch of promoter usage between normal breast tissue and cancer tissue. It is thought that in normal breast tissue, the function of promoters I.3 and II is suppressed through the binding of EAR-2, COUP-TFI, and EARgamma to S1, and through the binding of Snail/Slug proteins to their binding site that quenchs the CREaro activity. In cancer tissue, the expression levels of EAR-2, COUP-TFI, EARgamma, Snail, and Slug decrease, and aromatase expression is then up regulated through the binding of ERRalpha-1 to S1 and the binding of CREB or related factors to CREaro. Results from this and other laboratories reveal that aromatase activity in aromatase expressing cells can also be modified by treatment with aromatase inhibitors and the antiestrogen ICI 182, 780. While aromatase inhibitors are used to treat breast cancer, the treatment has been found to increase the level of aromatase in the breast tissue of some patients. The enhancement of aromatase activity by aromatase inhibitors is thought to be due to a decrease of aromatase protein degradation by enzyme-inhibitor complex formation, up-regulation of the aromatase gene transcription through a cAMP-mediated mechanism, and an induction of aromatase expression by gonadtropins that are released from the pituitary in response to a reduction of estrogen levels in circulation in premenopausal women. Antiestrogen ICI 182, 780 has been found to suppress aromatase expression, but the mechanism has not yet been determined. In addition, aromatase activity and expression can be affected by environmental chemicals. A detailed structure-function study has revealed that flavones, but not isoflavones, are inhibitors of aromatase. It was found that flavones bind to the active site of aromatase in an orientation in which their rings-A and -C mimic rings-D and -C of the androgen substrate. The modulation of aromatase expression by endocrine disrupting chemicals is exemplified by two organochlorine pesticides (i.e. toxaphene and chlordane) that have been found to be antagonists of ERRalpha-1 orphan receptor. These compounds reduce ERRalpha-1 activity, resulting in a suppression of aromatase expression.

It has long been proposed that selective binding of histone H1 is, in part, responsible for the differential developmental regulation of the oocyte and somatic 5S rRNA genes in Xenopus laevis. In this study we show that histone H1 binds both oocyte and somatic genes equally after reconstitution into mononucleosomes or oligonucleosome arrays. Furthermore, we show that the binding of histone H1 selectively represses only oocyte gene transcription and that an RNA polymerase III transcription complex is able to initiate transcription of nucleosomal somatic templates regardless of whether histone H1 is present. These results support a model in which the differential regulation of the 5S rRNA genes is not simply due to the prevention of histone H1 binding by transcription complexes on the somatic genes, but rather to a difference in the histone H1 interaction with the somatic and oocyte genes.

In an attempt to understand the mechanism by which transcription factors compete with histone octamers for cognate binding sites in chromatin, the effect of the histone binding protein nucleoplasmin on the binding of TFIIIA to nucleosomal 5S rRNA genes was tested. In this study, it was shown that, despite the previously reported nucleosome remodeling ability of nucleoplasmin, the binding of TFIIIA to nucleosomal DNA cannot be facilitated by this protein. Furthermore, it was demonstrated that nucleoplasmin cannot overcome nucleosome mediated repression of transcription of reconstituted 5S rRNA genes. In contrast to earlier work, this study used a homologous system composed of the 5S rRNA gene, nucleoplasmin, and TFIIIA from Xenopus laevis.

Experimental study on the operators' cognitive activities had been performed using nuclear power plant simulator. The specific feature of the present study is that the state of the operator during the interaction through the man-machine interface is analyzed based on the diverse information; 1) Estimated cognitive state,2)Estimated mental work load,3) Operational sequence history, 4)Questionnaire and 5)Video record. These informations are integrated and graphically represented on the form of Chronological Diagram, by which the operators' dynamic cognitive behavior can be analyzed. Results of the simulator experiments, in which three expert operator participated, demonstrated that the present method can provide the valuable information concerning the operators' cognitive behavior during the task of anomaly diagnosis.

Computer simulation was performed on a cognitive experiment of abnormal event identification in a nuclear power plant. The process of identification has been modeled as similarity matching of symptomatic patterns and hypothesis validation by symptom observation. As a result of comparison, the simulation could explain behaviors of the subjects generally well, and some characteristics of operator's cognitive processes have been revealed.

An integrated software system has been under development which aims at analyzing and evaluating the effectiveness of man-machine system design, by computer simulations from various viewpoints of human-factors. In this paper, the configuration of a distributed simulation system is first introduced, followed by an explanation of how the operator simulator model is organized by a Petri net model. Also presented is an example simulation of a plant anomaly diagnoses procedure using the Petri net model in its current state of development in the initial phase of software development.

A total of three TR-I test rockets, about one-quarter size of the Japanese H-U launch vehicle, were launched in 1988 and in 1989. External and internal acoustic environments as well as vibration response of the nose fairing were measured during the ascent of each rocket. It is found that the external sound or fluctuating pressure level of the fairing is high both at lift-off and at transonic flight. However, with regard to the internal sound pressure level and the acceleration level of the fairing structure, they are high at lift-off but relatively low at transonic flight. The noise reduction (NR) and the vibration response of the structure for the rocket exhaust noise at liftoff are similar to those measured by acoustic tests in a reverberation chamber.

The purpose of this study was to determine if perospirone, a second generation antipsychotic drug and partial agonist at serotonin-5-HT1A receptors, enhances electrophysiological activity, such as event-related potentials (ERPs), in frontal brain regions, as well as cognitive function in subjects with schizophrenia. P300 current source images were obtained by means of standardized low resolution brain electromagnetic tomography (sLORETA) before and after treatment with perospirone for 6 months. Perospirone significantly increased P300 current source density in the left superior frontal gyrus, and improved positive symptoms and performance on the script tasks, a measure of verbal social cognition. Perospirone also tended to enhance verbal learning memory in patients with schizophrenia. There was a significant correlation between the changes in P300 amplitudes on the left frontal lead and those in social cognition. These results suggest the changes in three-dimensional distribution of cortical activity, as demonstrated by sLORETA, may mediate some of the actions of antipsychotic drugs. the distinct cognition-enhancing profile of perospirone may be related to its actions on 5-HT1A receptors.

Piezoelectric polymers have large dielectric and mechanical internal losses. In this study, we introduced internal losses into Mason's equivalent circuit, and analyzed the effects of these losses on the transducer response, mainly in the frequency domain. To prove the validity of the theoretical analysis, we fabricated polymer transducers of several backing load types which are effective for practical use, using vinylidene fluoride and trifluoroethylene copolymer films, and evaluated their frequency and impulse responses. The experimental results are in good agreement with the theoretical prediction. We conclude that a consideration of the internal losses is essential for the proper design and correct evaluation of polymer transducers.

OMATA, K., OTSUKA, Y., CHIBA, S., ITOH, T., GOTOH, T., IMAI, Y., SAKURAI, Y., SATOH, M., HARUYAMA, T., HIWATARI, M., SATOH, K., KAITOH, A., ABE, K. and YOSHINAGA, K. Indomethacin Does Not Attenuate the Hypotensive Effect of Captopril, a Converting Enzyme Inhibitor in Goldblatt Hypertensive Rats. Tohoku J. exp. Med., 1981, 134 (1), 9-19-Whether or not prostaglandins (PGs) have anything to do with the hypotensive effect of a converting enzyme inhibitor, Captopril (SQ 14, 225), was studied in two kidney one clip Goldblatt hypertensive rats. Four to 10 weeks after clipping the left renal artery of male Splague-Dawley rats, 50mg/kg of captopril (Group 1, n=7) or 12.5mg/kg of indomethacin (Group 2, n=7) were infused for 4hr under the conscious state. For the subsequent 4hr, both 50mg/kg of captopril and 12.5mg/kg of indomethacin were infused in both groups of rats. Mean blood pressure (MBP) was recorded continuously. Plasma renin activity (PRA) and urinary excretion rate of PGE (UPGE) were measured by radioimmunoassay. Urinary sodium (UNa) and potassium (UK) excretions were measured by a flame photometer. After captopril infusion the pressor response to the injection of 100ng of angiotensin I decreased from 29.1± 4.2 to 4.8±1.6mmHg, and that of angiotensin II increased from 35.9±3.6 to 75.0±5.1mmHg (p

In spontaneously hypertensive rats, we studied the participation of xanthine oxidase-linked free radical in ischemia and reperfusion-induced cerebral injury, using allopurinol, a xanthine oxidase inhibitor. The loss of righting reflex was noted in some animals after a 4 hour occlusion of bilateral common carotid arteries and 19 of 25 animals died within 72 hours after reperfusion. One hour after reperfusion, the cerebral water content increased significantly, with an increase in sodium content and a decrease in potassium content. In 7 animals treated with oral administrations of allopurinol (200 mg/kg) 24 hours and 1 hour before occlusion, no death was found either during occlusion or after reperfusion, and the loss of righting reflex was noted in only one animal 24-72 hours following reperfusion. The increase in cerebral water content and accompanied changes in electrolyte contents were clearly prevented by allopurinol. These results suggest the possibility that the production of xanthine oxidase-linked free radical participates in cerebral injury due to ischemia and reperfusion in spontaneously hypertensive rats.

The WC-Co alloys coated with TiN by chemical vapour deposition process are substantially improved in their wear resistive properties, but are deteriorated in the failure resistance in comparison with those of the same alloys coated by physical vapour deposition process.When the residual stress of WC-Co alloys coated with TiN by CVD or PVD process was measured by X-ray method, the residual stress of the CVD coated alloys was tensile, while that of the PVD coated alloys was compressive.To estimate the effects of these residual stresses on the strength of the TiN-coated alloys, transverse-rupture strength was measured, and the crack sensitivity was also examined from the crack length around a Rockwell hardness indent. Owing to the residual stress of tension in the CVD coated alloys, the crack sensitivity increased and the fracture strength decreased.When the PVD coated alloy was annealed at a temperature above 1173K, the residual stress of compression changed to tensile stress and the crack sensitivity increased. To make clear the cause of the change of these residual stresses in TiN-coated alloys, X-ray diffraction patterns were measured by use of Co Kα radiation monochromated by a graphite monochrometer, and furthermore, the crystalline states of the coated layer, the substrate and the interfacial phases were investigated by EPMA.

再開発で造成した広場について、環境と調和し品格のある緑の場を構成する (二とを目指し、5年後に予定された鳥取国体開催時を初期育成の目標期として集約的な管理を行い、ほぼ目標を達成Lた。しかし、この間に、基礎L、上質、気象特性、肥培管理、植・栽組合せ等にかかわる多くの問題に直面し、その都度に工夫を要した1当初目標を達成した現時点で、仕上りと、問題点や対策を紹介して今後の参考とする。

The role of endogenous prostaglandins in the antihypertensive mechanism of orally active angiotensin I-converting enzyme inhibitor in low renin hypertension was investigated. In the SQ 14225-responders with low renin hypertension, blood pressure was elevated to control level and antihypertensive effect of SQ 14225 was attenuated after the inhibition of endogenous prostaglandin synthesis with indomethacin, while no significant change in blood pressure was found in the SQ 14225-responders with normal renin hypertension. Urinary prostaglandin E excretion was not significantly increased after the SQ 14225 administration but significantly decreased after the administration of indomethacin. There was no significant difference in urinary prostaglandin E excretion between normal renin hypertension and low renin hypertension. These results suggest that SQ 14225 may potentiate extrarenal vasodilating prostaglandin system, probably vascular prostaglandin system, contributing to the antihypertensive mechanism in SQ 14225-responders with low renin hypertension. The augmented renin release following SQ 14225 administration was inhibited by indomethacin, suggesting that endogenous prostaglandin system may contribute to the negative short feedback mechanism of renin release.

The present study was done to investigate the role of endogenous prostaglandins in the mechanism of renin release stimulated by angio-tensin I-converting enzyme inhibitor, SQ 14225 in 9 hypertensive patients and 3 normotensive subjects. Plasma renin activity was significantly i increased after the administration of SQ 14225 and decreased to control levels after the addition of indomethacin. Pre-treatment with indomethacin also inhibited the augmentation of renin release following the SQ 14225 administration. Urinary excretion of prostaglandin E was not significantly increased after the SQ 14225 administration but significantly decreased after the administration of indomethacin. The present data that the augmented renin release due to the suppression of the negative short feedback mechanism of renin release by SQ 14225 was inhibited by indomethacin suggest that endogenous prostaglandin system may contribute to the short feedback mechanism of renin release.

The present study was done to investigate the interrelationships between renal kallikrein-kinin, renal prostaglandin E and renin-angiotensin-aldosterone systems in human and the possibility that renal kallikrein-kinin and renal prostaglandin E may participate in the pathogenesis of essential hypertension by means of measuring urinary excretion of kallikrein and prostaglandin E, plasma renin activity and plasma aldosterone concentration before and after stimulation or inhibition of the renin-angiotensin-aldosterone system and inhibition of renal prostaglandin E generation. Urinary kallikrein excretion was increased after the stimulation of the renin-angiotensin-aldosterone system by low Na diet or the administration of furosemide and upright posture, while it tended to decrease after the inhibition of the renin-angiotensin-aldosterone system by the administration of 1-sarcosine-8-isoleucine angiotensin II under sodium depletion or spironolactone. These data showed that the changes in urinary kallikrein excretion paralelled with those of the renin-angiotensin-aldosterone system following various stimuli, suggesting that renal kallikrein-kinin system may regulate blood pressure by opposing the action of the renin-angiotensin-aldosterone system. Urinary PGE excretion was decreased after sodium depletion and increased after the administration of furosemide in spite of the augmentation of the renin-angiotensin-aldosterone system. The changes in urinary PGE excretion was closely related to those in urinary Na output after various stimuli and a significant positive correlation was found between basal levels of urinary PGE and those of urinary Na, suggesting that renal prostaglandin E may be involved in the regulation of blood pressure by affecting renal sodium handing. The present data showed that basal level of urinary excretion of PGE and kallikrein was lower in essential hypertension than in normal subjects and that the release of renal kallikrein and PGE after furosemide administration was also suppressed in essential hypertension compared with that in normal subjects, suggesting that there exists an impaired defense mechanism against the renin-angiotensin-aldosterone system resulting in sodium retention.

Estimation of urinary kininogenase activity by radioimmunoassay of generated kinin was studied. Bovine serum low molecular weight kininogen was proved not to cross-react with kallidin antibody and also bradykinin antibody. This kininogen was used as substrate measuring urinary kininogenase activity. Separation of released kinin from the kininogen was not required in the present method. Urinary kallikrein activity was found to be significantly decreased in essential hypertension, in chronic glomerulonephritis and in patients who had received renal transplantation. On the contrary, an increase in urinary kallikrein was found in primary aldosteronism and in Bartter’s syndrome. The present method was very useful for measuring kininogenase activity.

The present study shows that there is a circadian variation in the excretion of urinary kinin, kallikrein and prostaglandin E (PGE) as well as urine flow, urinary sodium excretion and urinary potassium excretion in recumbent healthy volunteers. The present data, that the acrophase of urinary kallikrein excretion was 1.5 hr later than that of plasma aldosterone concentration (PAC) and that a significant positive correlation was found in circadian variations between urinary kallikrein and PAC, suggest that the circadian variation of urinary kallikrein excretion may be regulated by aldosterone. The pattern of circadian variation of average urinary kinin excretion coincided with those of average urine flow, urinary sodium excretion and urinary PGE excretion, suggesting that renal kinin and PGE may be involved in the regulation of water-sodium excretion. The present data that the phase of circadian variation of urinary kinin was delayed from that of urinary kallikrein and that there was a mirror image between the circadian variation in urinary kinin and kallikrein suggest that there may be a feedback mechanism in renal kallikrein-kinin system.

During embryonic life the thymic rudiment is extensively seeded by invading hemopoietic precursors that give rise to mature T cells (1). In birds thymus, colonization by precursor cells is limited to two defined time periods of embryonic development (2). The first hemopoietic precursor cells appear at day 5 in the thymus of quail embryos. At this stage of development the precursors were enriched in the perithymic region. These precursors are often in contact with endothelial cells of the jugular vein, a prefered site of extravasation; they are also dispersed within the mesenchymal tissue around the thymus, and adhere to the basal lamina that separates the thymus from the mesenchyme (3).

Monoamine metabolites and norepinephrine (NE) in the cerebrospinal fluid of patients with cerebrovascular dementia were measured to study the effects of administration of idebenone. Six patients with cerebral infarction and one with cerebral hemorrhage (mean age 65.4 years) were enrolled as subjects. All the patients had mental and intelligence impairment which was evaluated by the Hasegawa's Dementia Rating (DR) Scale. The patients were medicated with a 90 mg/day dose of idebenone for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and NE in the cerebrospinal fluid were determined by high-performance liquid chromatography before and after the medication of idebenone. Before the medication, the level of HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly lower (p less than 0.01) as compared with that in control subjects of similar age. The level of 5-HIAA was 18.5 +/- 2.7 ng/ml, and that of MHPG 9.5 +/- 0.7 ng/ml, both of which were lower than those of the controls, though statistically not significant. NE was similar to the control value. After administration of idebenone, HVA measured was 27.1 +/- 3.2 ng/ml, showing a tendency to increase. The levels of 5-HIAA and MHPG were 26.7 +/- 2.3 ng/ml and 10.7 +/- 0.6 ng/ml, respectively, which were significantly (p less than 0.05) higher than the premedication values. The percentages of the change were 12.8 +/- 8.0 for HVA, 58.2 +/- 18.5 for 5-HIAA and 14.2 +/- 5.0 for MHPG. The score of the DR scale was improved by 5 or less after the idebenone medication in most subjects. HVA and 5-HIAA increased markedly in the patients who showed a tendency of improvement of mental impairment as evaluated by the DR scale. The results suggested that idebenone would improve abnormalities in neurotransmitters of patients with cerebrovascular dementia, especially promoting serotonin turnover.

Antiestrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. To investigate the effects of these drugs on gene expression in breast cancer cells, we treated estrogen receptor–positive MCF-7 cells stably transfected with the aromatase gene (known as MCF-7aro cells) with testosterone, 17β-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an antiestrogen (tamoxifen). We found that testosterone or 17β-estradiol induced the proliferation of MCF-7aro cells at a rate six times faster than the untreated cells. In addition, the testosterone-induced proliferation of MCF-7aro cells was effectively suppressed by letrozole, anastrozole, or tamoxifen. Microarray analyses on Affymetrix Human Genome U133A GeneChips (Affymetrix, Santa Clara, CA) were carried out using total RNA isolated from the control and treated cells. At the false discovery rate of 0.05 and a minimum fold-change criteria of 1.5, 104 genes were identified that were up-regulated and 109 genes were identified that were down-regulated by both androgen and estrogen. More than 50% of these hormone-regulated genes were counterregulated by all three inhibitors and >90% were counterregulated by at least one of the inhibitors. Comparing the effect of each inhibitor on gene expression, we observed that letrozole and anastrozole are more similar in terms of the genes they affect compared with treatment with tamoxifen. To validate the gene expression profiles identified from microarray analyses, the expression patterns of 13 representative genes were examined by Northern analysis. Finally, the genes identified as statistically significant were classified based on their expression patterns and biological function/pathways. The results of this study provide us with a better understanding of the actions of both aromatase inhibitors and antiestrogens at the molecular level. We believe that the results of this study serve as the first step in identifying unique expression patterns following drug treatment, and that this will ultimately be useful in customizing patient treatment strategies for hormone-dependent breast cancer.

The changes of active and inactive renin in plasma after the oral administration of 25 mg or 50 mg of SQ 14225 (Captopril) were studied in 29 hypertensive patients. Inactive renin was calculated as plasma renin activity (PRA) after cold storage minus PRA before cold storage. The patients were divided into 2 groups, responders and non-responders, according to the response of active renin to Captopril. In 9 responders, the active renin increased markedly while the inactive renin decreased. On the other hand, in 20 non-responders, both renin activities increased only slightly. These results suggest that inactive renin may be converted in vivo to active renin by Captopril.

The antihypertensive mechanism of orally active angiotensin I-converting enzyme inhibitor, SQ 14225 (SQ), in low renin hypertension was investigated. In the SQ-responder with low renin hypertension, the hypotensive effect of SQ was abolished after the inhibition of endogenous prostaglandin (PG) synthesis with indomethacin, while no significant change in blood pressure was found in the SQ-responder with normal renin hypertension. These results suggest that SQ may potentiate the vasodilating PG system, contributing to the antihypertensive mechanism in SQ responders with low renin hypertension.

Piezoelectric polymers have large dielectric and mechanical internal losses. In this study, we introduced internal losses into Mason's equivalent circuit, and analyzed the effects of these losses on the transducer response, mainly in the frequency domain. To prove the validity of the theoretical analysis, we fabricated polymer transducers of several backing load types which are effective for practical use, using vinylidene fluoride and trifluoroethylene copolymer films, and evaluated their frequency and impulse responses. The experimental results are in good agreement with the theoretical prediction. We conclude that a consideration of the internal losses is essential for the proper design and correct evaluation of polymer transducers.